Parkinson's Disease: A Network Disorder Affecting Body and Mind

Parkinson's disease does more than cause tremor and trouble walking. It can also affect sleep, smell, digestion and even thinking. That may be because the disease disrupts communication in a brain network that links the body and mind, a team reports in the journal Nature.

"It almost feels like a tunnel is jammed, so no traffic can go normally," says Hesheng Liu, a brain scientist at Changping Laboratory and Peking University in Beijing and an author of the study.

The finding fits nicely with growing evidence that Parkinson's is a network disorder, rather than one limited to brain areas that control specific movements, says Peter Strick, a professor and chair of neurobiology at the University of Pittsburgh who was not involved in the study.

Other degenerative brain diseases affect other brain networks in different ways. Alzheimer's, for example, tends to reduce connectivity in the default mode network, which supports memory and sense of self. ALS (amyotrophic lateral sclerosis) primarily damages the motor system network, which controls movement.

Understanding the network affected by Parkinson's, which affects about 1 million people in the United States, could change the way doctors treat the disease. People with Parkinson's often have symptoms that vary in ways that are hard to explain. For example, someone who usually is unable to stand may suddenly leap when faced with an emergency. And Parkinson's patients who can still walk may freeze if they try to carry on a conversation.

"So you know that their movement problems [are] not simply related to their motor circuits," Liu says, but also to circuits involved in thinking and emotion.

For decades, scientists struggled to explain how these circuits are linked. Then in 2023, a team led by researchers at WashU Medicine in St. Louis discovered a brain network that does seem to connect movement and thinking. They named it the somato-cognitive action network, or SCAN. And Liu's team thought it might explain some of the odd symptoms seen in Parkinson's.

So they used MRI data on more than 800 brains to compare the SCAN networks in healthy people with those in Parkinson's patients. The team found that patients had abnormally strong connections between the SCAN network and brain areas known to be affected by their disease.

Instead of making communication better, Liu says, those strong connections were causing a traffic jam that kept signals from getting through.

Next, Liu's team looked to see what happened to the SCAN network when people with Parkinson's got deep brain stimulation — a treatment that delivers pulses of electricity to areas affected by the disease. "When the stimulator is turned on, the connectivity was immediately lowered," Liu says, allowing brain traffic to flow normally again.

To see how other treatments altered the SCAN network, the team studied patients receiving the drug levodopa, transcranial magnetic stimulation, and focused ultrasound stimulation. "All these effective treatments are actually acting on this same circuitry," Liu says, "and the effect is, remarkably, identical."

The finding is just the latest to show how the conventional wisdom about Parkinson's has changed. "In the past, people thought of Parkinson's disease as the classic movement disorder," Strick says. "But it's clear now that multiple systems are involved."

People with Parkinson's often describe symptoms that go far beyond problems with voluntary movement, such as tremor, slurred speech and a shuffling gait. Lesser known symptoms include chronic constipation, a reduced sense of smell, sleep disorders, memory lapses and fatigue — all of which involve brain systems with no direct link to voluntary movement.

This sometimes unpredictable mix of symptoms can be misinterpreted in a way that feels stigmatizing to patients, doctors say. Strick recalls one man whose early symptoms included a sudden drop in blood pressure when he stood up. "He would fall down, unexplainably, and people thought he was a drunk," Strick says, adding that the man was actually pleased when he got a medical diagnosis that explained his behavior.

The new study appears to explain odd symptoms like that, Strick says. They're occurring, he says, because the SCAN network includes brain areas that normally control involuntary functions, like heart rate, digestion and blood pressure. SCAN areas also include those that affect REM sleep, and certain types of memory and thinking.

Current treatments for Parkinson's don't fix these non-motor problems, Liu says. But future ones might, he says, by targeting overlooked areas in the brain's SCAN network.